Background: Health literacy can be considered as a factor affecting healthcare providers' decision-making. The aim of this study was to investigate health literacy status and its relationship with quality of life among the nurses working in teaching hospitals affiliated with Shiraz University of Medical Sciences in Iran. Materials and Methods: This cross-sectional study was conducted in 2017. To this end, 185 nurses from hospitals were selected by stratified random sampling. The data collection instruments included the standardized Health Literacy Questionnaire and the 36-Item Short Form Health Survey. The data were analyzed through descriptive statistics as well as t test, analysis of variance, Pearson correlation coefficient, and multivariate linear regression analysis using SPSS23 (α = 5%). Results: The mean scores for health literacy and quality of life were 70.06 (12.98) and 60.86 (17.26), respectively. A significant relationship was observed between the health literacy and quality of life (p <0.001), Access (p = 0.004), reading skills (p = 0.004), understanding (p = 0.016), and application of health information (p = 0.012) as the dimensions of health literacy were identified among the predictors of quality of life. In addition, there was a significant relationship among age (r = 0.22, p = 0.008), work experience (r = 0.27, p = 0.002), and employment relationship (F = 3.89, p = 0.005) and the mean score for nurses' health literacy status. Conclusions: A significant relationship was observed between health literacy and quality of life in nurses. Healthcare policy-makers are suggested to take measures to develop programs on promoting health literacy and related skills to improve the status of quality of life among nurses.